One of the most complex and difficult problems that has plagued the medical profession and pharmaceutical industry for decades is the problem of achieving a therapeutic concentration of a drug locally at a target site within the body without producing unwanted systemic side effects. Parenteral or oral therapy of substances directed at treating disease in a particular internal organ must often be given in amounts dependent upon achieving critical systemic blood levels that can produce devastating side effects at other areas in the body. A prime example of a situation where local therapy is needed with drugs that also produce unwanted systemic side effects is the prevention of complications following the placement of a cardiovascular prosthetic device such as a prosthetic vascular graft, patch, or stent used to repair a damaged vessel.
Graft or stent failure is often associated with the inherent thrombogenicity of the blood contacting surface of the prosthetic device and with the body's own repair mechanisms which can lead to progressive stenotic occlusion due to neointimal fibrosis and hyperplasia. Systemic therapy aimed at preventing coagulation and thrombosis locally at the graft site is often complicated by bleeding at other sites. Likewise, systemic treatment with growth mediators or chemotherapeutic agents can produce a hyperplastic or hypoplastic response in tissue not specifically targeted. Similarly, administration of vasodilators can produce systemic hypotension.
There have been many attempts to render the vascular grafts themselves less thrombogenic, e.g., by coating the luminal surface of the graft with non-thrombogenic polymers (U.S. Pat. No. 4,687,482), cells (U.S. Pat. No. 5,037,378) or with anticoagulant drugs in a polymer coating (PCT Application WO 91/12279). Although these attempts have improved the success associated with graft placement, complications with clotting, thrombosis, and restenosis, especially that seen due to fibroplasia and smooth muscle proliferation, still abound.
Likewise, there have been many attempts to effectuate local drug delivery via endovascular means. Percutaneous transluminal coronary angioplasty (PTCA) balloon dilation catheters have been designed with coatings of drugs on the external surface of the balloon (e.g., U.S Pat. Nos. 5,102,402 and 5,199,951). Other PTCA catheters contain perforations in the wall of the PTCA balloon for infusion of drugs such as the Wolinsky catheter or the balloon within a balloon design seen in U.S. Pat. No. 5,049,132. These catheters, however, often disrupt blood flow and reduce distal tissue perfusion. Other catheters such as the Stack perfusion catheter and the catheter embodied in U.S. Pat. No. 5,181,971 were designed to facilitate drug delivery without disrupting distal tissue perfusion. These devices, however, are limited in their clinical applications, are bulky, and cannot be anchored in the vessel proximal to the targeted treatment area or utilized in non-vascular applications.
Therefore, there exists a need in the art for a means and a method of providing local therapy which can sustain high local concentrations of therapeutic drugs at a predetermined site, e.g., a site of vessel repair, without producing unwanted systemic side effects. There especially exists a need for a method and a device which can provide minimal concentrations of therapeutic agents directly to the boundary layer of blood flow near the vessel wall just proximal to a targeted treatment area which greatly reduces the amount of drug needed to achieve a therapeutic result at the target area without substantially compromising central blood flow through the vessel.
There also exists a need to provide effective local therapy for treatment of cancer and other diseases in many areas of the body such that the chemotherapy can be localized to targeted tissues, thereby minimizing the amount of drug needed for treatment and thus preventing unwanted systemic side effects from systemic administration.